[Marjolin's ulcer associated with verrucous carcinoma in an immunocompromised patient]. / Úlcera de Marjolin asociada a carcinoma verrugoso en paciente inmunocomprometido.

Background: Marjolin's ulcer is the malignant degeneration of any chronic wound, with a latency period from tissue injury to variable malignant transformation that may occur up to 30 years later. Among the associated neoplasms, squamous cell carcinoma (SCC) is the predominant lineage in up to 71% of cases. The verrucous carcinoma variant has been estimated to have a low presentation, being described in the literature as 2% of all SCC and reported anecdotally in immunosuppressed patients, which justifies the objective of this publication. Clinical case: 65-year-old female patient with a history of being a carrier of human immunodeficiency virus (HIV) infection, who presented a verrucous carcinoma associated to a Marjolin ulcer secondary to herpes zoster and infection of soft tissues in the right leg, with a latency period of 10 years from the initial infectious process to histopathological confirmation. Conclusions: The finding of a verrucous carcinoma on a Marjolin ulcer has been little described in literature, with a lower incidence in the context of a patient with a history of being a carrier of HIV infection, finding 7 case reports, the oldest from 1998. For this reason, it is important to have diagnostic suspicion, to carry out an adequate study protocol and always making clinical-pathological correlation, in order to establish timely and individualized treatment.

Introducción: la úlcera de Marjolin es la degeneración maligna de cualquier herida crónica, con un periodo de latencia desde la lesión tisular a la transformación maligna variable que puede presentarse hasta 30 años después. De las neoplasias asociadas, el carcinoma espinocelular es la estirpe predominante hasta en 71% de los casos. La variante de carcinoma verrugoso se ha estimado con una presentación baja, pues ha sido descrito en la literatura como el 2% de todos los carcinomas espinocelulares y reportado de manera anecdótica en pacientes inmunosuprimidos, lo que justifica el objetivo de esta publicación. Caso clínico: mujer de 65 años con el antecedente de ser portadora de infección por virus de inmunodeficiencia humana (VIH), que presentó un carcinoma verrugoso asociado a una úlcera de Marjolin secundaria a herpes zóster e infección de tejidos blandos en pierna derecha, con un periodo de latencia de 10 años desde el proceso infeccioso inicial hasta la confirmación histopatológica. Conclusiones: el hallazgo de un carcinoma verrugoso asentado sobre una úlcera de Marjolin ha sido poco descrito en la literatura, con una menor incidencia en el contexto de un paciente con antecedente de ser portador de infección por VIH, ante lo cual encontramos 7 reportes de caso, el más antiguo de 1998. Por este motivo es importante contar con la sospecha diagnóstica, para poder hacer un protocolo de estudio adecuado y siempre haciendo correlación clínico-patológica, con la finalidad de instaurar un tratamiento oportuno e individualizado.

Dermatosis más frecuentes en pacientes con trasplante renal.

OBJECTIVE: To determine the most frequent dermatoses in patients with kidney transplant in the dermatology consultation, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, in Mexico City, in the period from March 2016 to March 2020. METHOD: Descriptive, cross-sectional study that included 153 patients with a complete medical history with prior informed consent and authorization from the hospital ethics committee. RESULTS: All patients presented one or more dermatoses. The most frequent were infectious (mycosis, viral) and, in decreasing order, other dermatoses (keratosis pilaris, melasma), tumorous (benign), inflammatory (seborrheic dermatitis, eczema), probably secondary to drugs and autoimmune (alopecia areata). CONCLUSIONS: All kidney transplant patients presented at least one dermatosis, predominantly those of infectious origin. We recommend dermatological evaluation prior to transplantation for timely diagnosis and treatment of dermatoses that could increase the morbi-mortality of patients.

OBJETIVO: Determinar las dermatosis más frecuentes en pacientes con trasplante renal en la consulta de dermatología del Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, en Ciudad de México, en el período de marzo de 2016 a marzo de 2020. MÉTODO: Estudio descriptivo, transversal que incluyó 153 pacientes con historia clínica completa, previo consentimiento informado y autorización del comité de ética del hospital. RESULTADOS: Todos los pacientes presentaron una o más dermatosis. Las más frecuentes fueron las infecciosas (micosis, virales) y, en orden decreciente, otras dermatosis (queratosis pilar, melasma), tumorales (benignas), inflamatorias (dermatitis seborreica, eccemas), probablemente secundarias a fármacos y autoinmunitarias (alopecia areata). CONCLUSIONES: Todos los pacientes receptores de trasplante renal presentaron al menos una dermatosis, predominando las de origen infeccioso. Recomendamos una valoración dermatológica previa al trasplante para el diagnóstico y el tratamiento oportuno de las dermatosis que podrían aumentar la morbimortalidad de los pacientes.

NLRP3 Regulates IL-4 Expression in TOX+ CD4+ T Cells of Cutaneous T Cell Lymphoma to Potentially Promote Disease Progression.

In cutaneous T cell lymphoma (CTCL), a dominant Th2 profile associated with disease progression has been proposed. Moreover, although the production and regulation of IL-4 expression during the early stages of the disease may have important implications in later stages, these processes are poorly understood. Here, we demonstrate the presence of TOX+ CD4+ T cells that produce IL-4+ in early-stage skin lesions of CTCL patients and reveal a complex mechanism by which the NLRP3 receptor promotes a Th2 response by controlling IL-4 production. Unassembled NLRP3 is able to translocate to the nucleus of malignant CD4+ T cells, where it binds to the human il-4 promoter. Accordingly, IL-4 expression is decreased by knocking down and increased by promoting the nuclear localization of NLRP3. We describe a positive feedback loop in which IL-4 inhibits NLRP3 inflammasome assembly, thereby further increasing its production. IL-4 induced a potentially malignant phenotype measured based on TOX expression and proliferation. This mechanism of IL-4 regulation mediated by NLRP3 is amplified in late-stage CTCL associated with disease progression. These results indicate that NLRP3 might be a key regulator of IL-4 expression in TOX+ CD4+ T cells of CTCL patients and that this mechanism might have important implications in the progression of the disease.

Association of Pathogenic Th17 Cells with the Disease Severity and Its Potential Implication for Biological Treatment Selection in Psoriasis Patients.

Psoriasis is an inflammatory autoimmune disease characterized by cutaneous lesions in plaques. It has been proposed that the immune response has a key role in the disease progression. Particularly, the Th17 cells through IL-17 can contribute to maintain the inflammatory process. The pathogenic Th17 phenotype has been described in human diseases and associated with high severity in inflammatory experimental models. However, it is not clear if the pathogenic phenotype could be present in the skin and peripheral blood as well as its possible association to severity in psoriasis. In the lesional skin, we found high infiltration of Th17 cells and the pathogenic phenotype, finding a correlation between the frequency of Th17 cells and the Psoriasis Area and Severity Index (PASI) score. In peripheral blood, we observed a pool of Th17 lymphocytes with potential to acquire pathogenic features. Interestingly, the percentage of pathogenic Th17 cells (CD4+ RORγt+ IFN-γ +) correlates with disease severity. Moreover, we distinguished three groups of patients based on their IL-17/IFN-γ production by Th17 lymphocytes, which seems to be related with a dynamic or stable potential to express these cytokines. Remarkably, we evaluated the cytokine production by Th17 cells as an immunological marker for the adequate selection of biologic therapy. We found that patients analyzed by this immunological approach and treated with antibodies against IL-17 and TNFα showed great improvement depicted by reduction in PASI and Dermatology Life Quality Index (DLQI) score as well as the percentage of Body Surface Area (BSA). Altogether, our results highlight the importance of the assessment of the pathogenic phenotype in Th17 cells as an immune personalized analysis with the potential to support the therapy choice in the clinical practice.

[Mexican guidelines on the diagnosis and treatment of urticaria]. / Guía Mexicana para el Diagnóstico y el Tratamiento de la Urticaria.

BACKGROUND: Urticaria is a disease that a fifth of the population shallsuffer once in a lifetime. Recent clinical guidelines have proposed some fundamental changes in the diagnosis and treatment of urticaria, making the development of a national, multidisciplinary guideline, with wide acceptability among different professional groups -both specialists and primary health care workers-, necessary in Mexico. MATERIAL AND METHOD: Internationally recognized tools for guidelinedevelopment were used. An interdisciplinary group of clinical experts (some of them knowledgeable in methodology of guideline development) determined the objectives and scope of the Evidence Based Clinical Practice Guideline with SCOPE. It was decided to adapt and transculturize international guidelines on the diagnosis and treatment of urticaria. With AGREE-II three high-quality guidelines (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) were selected to function as basic guidelines (BG). A set of Clinical Questions was formulated that lead to recommendations/suggestions, based on these BG, taking into account the cultural and economic background of Mexico, according to GRADE recommendation development. RESULTS: By a formal process of discussion and voting during several working-sessions, experts and first level healthcare physicians determined the wording of the final guideline, taking particularly care of developing a document, adjusted to the reality, values and preferences of the Mexican patients. The use of oral second generation, non-sedating antihistamines as first line treatment is emphasized. CONCLUSION: This document is an Evidence Based Clinical Practice Guideline for the diagnosis and treatment of acute and chronic urticaria, based on three, high quality, international guidelines. It was developed by a multidisciplinary group. Tables and algorithms make the guideline user-friendly for both, first line health care physicians and specialists.

Antecedentes: la urticaria es una enfermedad que padece una quinta parte de la población en algún momento de su vida. Las guías internacionales recientes han propuesto unos cambios de fondo en su diagnóstico y tratamiento, por lo que había la necesidad de crear una guía nacional y multidisciplinaria, con base amplia en los gremios de especialistas y médicos de primer contacto en México. Material y método: un grupo interdisciplinario de expertos clínicos y algunos expertos en metodología determinó los objetivos y alcances de la Guía de Práctica Clínica Basada en Evidencia con el instrumento SCOPE. Se decidió llevar a cabo la adaptación y transculturización de guías internacionales para el diagnóstico y tratamiento de urticaria. Con el instrumento AGREE-II se seleccionaron las tres guías de alta calidad, como guías base (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) para formular y contestar la preguntas clínicas clave, en el contexto cultural y económico mexicano, según el método de desarrollo de recomendaciones GRADE. Resultados: mediante un proceso formal de discusión y votación durante varias juntas de expertos, se terminó la redacción de la forma final de la guía, con especial cuidado de lograr un ajuste a las realidades, valores y preferencias de los pacientes de México. Se hace hincapié en la administración de antihistamínicos vía oral de segunda generación, como tratamiento de primera elección. Conclusión: este documento es una Guía de Práctica Clínica Basada en Evidencia para el diagnóstico y tratamiento de urticaria aguda y crónica, basada en tres guías internacionales de alta calidad. Se desarrolló por un grupo multidisciplinario. Los cuadros y algoritmos hacen a la guía amigable para su uso por médicos de primer contacto y por especialistas.

Altered morphology and distribution of cellular junction proteins in non-lesional psoriatic epidermis: an insight into disease severity.

BACKGROUND: Psoriasis affects 2.7% of the world's population. Keratinocyte proliferation outside the basal layer suggests alterations in cell-cell interactions in affected epidermis. Anomalous expression of proteins forming intercellular junctions has been reported in lesional skin of psoriatic patients. In contrast, little is known about possible alterations in psoriatic non-lesional skin. METHODS: Ten clinically diagnosed psoriasis vulgaris patients and ten controls were studied. All patients were diagnosed with active but controlled psoriatic plates (PASI 3 to 5) and had not received any systemic treatment. The mean age was 43 years for patients and 43.5 years for controls. Four-mm2 skin samples were taken from lesional and non-lesional zones in patients and from abdomen in controls. Five-mum sections were examined for integrity and structural organization by fluorescent labeling of actin filaments and nuclei. Specific antibodies were utilized to localize occludin, E-cadherin, beta-catenin, and proliferation-specific keratins in sections and epidermal sheets. Samples were also processed for immunoblotting with occludin antibody. RESULTS: Lesional and non-lesional psoriatic epidermis from all patients showed keratinocyte hyperproliferation, lack of rete ridges and dermal papillae in the dermal-epidermal junction in some areas. Proteins forming tight and adherens junctions in non-lesional skin keratinocytes from two patients who during the course of the study evolved to uncontrolled disease, showed similar alterations to those observed in lesional skin of all the patients. However, the occludin isoforms expressed were apparently the same in all samples. CONCLUSIONS: Analysis of non-lesional skin in psoriatic patients diagnosed with controlled disease may provide clues about incipient structural abnormalities in the pathogenesis of psoriasis, providing an early diagnostic indicator for evolution to a generalized form of the disease.

[Mycoses frequency in three communities in the North mountain of the State of Puebla]. / Frecuencia de micosis en tres comunidades de la sierra norte de Puebla.

In order to know mycosis frequency in the North of the State of Puebla, Mexico, in habitants from the communities of Ayotoxco, Mazatepec and Zacatipan were studied. Previous medical study biological samples were submitted to direct examination, smear and culture. Histoplasmin and sporotrichin skin test were applied to 57 individual from Zacatipan. From 110 patients 146 mycological studies were performed. Eighty six cases (59%) of mycosis were detected: 43 finger or toenails onychomycosis, 25 tinea pedis, seven tinea capitis, four cases of tinea manum and, finally, five cases of seborrhoeic dermatitis and two of pitiriasis versicolor. We isolated: 18 streins of dermatophytes, mainly Trichophyton rubrum and T. mentagrophytes (11 and 5 strains respectively); 12 cultures of non-dermatophytes filamentous fungi; six cases of mycelia sterile; six yeast strains, most of them Candida spp but none C. albicans. From 57 patients to whom skin tests were applied, five of them (8.8%) were positive to both antigens; ten positive (17.6%) only to histoplasmin and eight (14%) to sporotrichin. This study showed that rural population from Puebla present a high frequency of superficial mycosis (61% of mycological studies). Considering the percentage of positive skin test we suppose that there are many not diagnosed sporotrichosis and histoplasmosis cases.